GENE AND VIRUS THERAPY SHARED RESOURCE PROJECT SUMMARY Mayo Clinic has a long-standing commitment to translating promising cancer therapies that benefit its patients to its clinical practice. The translation of new drugs, including promising virus-based therapies, from the cycles of basic and preclinical research to clinical trials requires expertise and facilities not often found in an academic setting. Thus, the initiation of the clinical trial process can be significantly delayed or completely blocked for the academic researcher/clinician. There are very few avenues that can be taken by the academic researcher/clinician to try and gain access to the necessary expertise and facilities. The Mayo Clinic Department of Molecular Medicine (DMM) established the necessary core resources on-site to translate virus- based research at the Mayo Clinic to Phase I and II clinical trials. The Mayo Clinic Cancer Center (MCCC) component of this resource, the Gene and Viral Therapy Shared Resource (GVTSR), was developed in conjunction with the MCCC Gene and Virus Therapy Program and provides MCCC members the broadest flexibility to access the complete range of expertise and services required for translation of a virus-based therapy to a clinical trial in an efficient and cost-effective manner. The GVTSR has developed the resources and expertise to manufacture large-scale clinical grade viral products, to conduct toxicological and pharmacological characterization of viral therapeutics in animal models, and to assure the quality of these activities. The GVTSR signature facility is the 2000 sq. ft. manufacturing facility of the Viral Vector Production Laboratory, with one GMP suite capable of up to 75 L virus production runs, and a preclinical suite for large- scale virus production process development. Additional laboratory space is dedicated to the Tox/Pharm Lab and QC functions, as well the availability of Mayo Clinic comprehensive animal facilities to support GVTSR needs. These GVTSR activities must be done using federally mandated practices (Good Laboratory Practices and Good Manufacturing Practices) that require specific personnel training, facilities, and quality control and quality assurance programs. The GVTSR has also developed a strong relationship with the FDA who has federal authority over these activities. The GVTSR can supply 2 of the major components of an IND application: the descriptions of the product manufacturing and safety testing, and the toxicology and pharmacology characterization of the product in appropriate animal models. Of equal importance are the capabilities of the GVTSR to develop large-scale viral production and purification processes to support preclinical studies as well as the manufacture of clinical grade product. The GVTSR works in close partnership with a clinician in the development and regulatory approval of a clinical trial protocol. This comprehensive approach has resulted in MCCC members translating multiple novel virus-based therapies to 13 Phase I and 2 Phase II clinical trials to treat 15 different tumor types.